Randomized phase II trial comparing folfirinox (5FU/leucovorin [LV], irinotecan [I] and oxaliplatin [O]) vs gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA). First results of the ACCORD 11 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4516-4516 ◽  
Author(s):  
M. Ychou ◽  
F. Desseigne ◽  
R. Guimbaud ◽  
M. Ducreux ◽  
O. Bouché ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Safety Data ◽  
Median Number ◽  
Tumor Location ◽  
Phase Iii ◽  
Expert Review ◽  
First Results

4516 Background: In a phase II trial of Folfirinox (F) in 35 MPA patients (pts), we reported a 26% response rate and median survival of 9.5 months (mo) with quality of life improvement (Conroy, JCO 2005). The aim of this phase II trial was to compare the response rate and safety of F vs G in pts with MPA. Methods: Chemotherapy-naïve pts aged 18–75 years with histologically or cytologically confirmed measurable MPA were randomized to receive G (1,000 mg/m2 IV weekly x 7 for 8 weeks [wks] then weekly x 3 out of 4 wks) or F (O 85mg/m2 d1 + I 180mg/m2 d1 + LV 400mg/m2 d1 followed by 5FU 400mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly). Patients were stratified by centre, performance status (ECOG 0 versus 1), and primary tumor location (head vs other). Primary endpoint was response rate. Results: From 01/05 to 11/06, all planned 88 pts (44 per arm) were enrolled. Median age was 56 yrs [35–76]. Currently, safety data for 81 pts (41F/40G) and efficacy data for 65 pts (31F/34G) are available (17 too early). One pt was ineligible in arm F. Two pts, one in each arm, did not receive protocol therapy. Median number of wks on treatment was 18 (F) and 7 (G). No toxic death occurred. Main grade 3–4 toxicities (arm F vs G) were G3 neutropenia (32%/17.5), G4 neutropenia (19.5%/0), G3–4 thrombocytopenia (12%/0), G3 vomiting (17%/2.5), G3 transaminases (0%/15) and G3–4 fatigue (27%/15).Confirmed partial responses (PR) rates (F/G) were 38.7% (12/31) and 11.7 % (4/34) according to the investigators and median duration of response was 6,3 and 4,6 mo. PR and stable disease (SD) were documented for 21/31 evaluable pts in arm F and expert review confirmed 13 PR (41.9 %) and 6 SD (19.3%). Conclusions: Folfirinox induces a response rate > 30% with manageable toxicity in ECOG 0–1 pts with MPA. According to these interim results, this trial will continue as a phase III study. Updated results will be presented at the meeting. Supported by a PHRC 2004 grant from the French Ministry of Health. [Table: see text]

Efficacy and safety of nivolumab (NIVO) in patients with advanced melanoma (MEL) and poor prognostic factors who progressed on or after ipilimumab (IPI): Results from a phase II study (CheckMate 172).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9524-9524 ◽  
Author(s):  
Dirk Schadendorf ◽  
Paolo Antonio Ascierto ◽  
John B. A. G. Haanen ◽  
Enrique Espinosa ◽  
Lev V. Demidov ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Safety Data ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label

9524 Background: In the phase III CheckMate 037 study, NIVO improved the objective response rate and progression-free survival with less toxicity vs chemotherapy in patients (pts) with MEL who progressed after prior IPI treatment. We report the first efficacy and updated safety data from pts with MEL in CheckMate 172, including those with rare melanoma subtypes (uveal, mucosal), brain metastases, or an ECOG performance status (PS) of 2. Methods: In this ongoing phase II, single-arm, open-label, multicenter study, pts with MEL who progressed on or after IPI were treated with NIVO 3 mg/kg Q2W for up to 2 years until progression or unacceptable toxicity (NCT02156804). We report efficacy and updated safety data from 734 treated pts with ≥1 year of follow-up (database lock: November 2016). Results: Of 734 pts, 50% had LDH>ULN, 7% ECOG PS 2, 66% M1c disease, 15% a history of brain metastases, and 23% received ≥3 prior therapies. Overall, 593 pts (81%) received more than 4 doses of NIVO. Overall, response rate at 12 weeks was 32%, with a complete response in 1% (Table). The 1-year overall survival (OS) rate was 63%. Any grade and grade 3/4 treatment-related adverse events (AEs) occurred in 66% and 17% of pts, respectively. Discontinuations due to treatment-related AEs occurred in 4% of pts. The most common treatment-related select (potentially immune-related) AEs were diarrhea (12%), hypothyroidism (9%), and pruritus (7%). Conclusions: CheckMate 172 is the largest study of NIVO efficacy and safety in pts with MEL who progressed on or after IPI. NIVO demonstrated a safety profile consistent with that of prior clinical trials. Efficacy outcomes were encouraging in some difficult-to-treat subgroups of pts with poor prognostic factors, such as mucosal melanoma and brain metastases. Clinical trial information: NCT02156804. [Table: see text]

Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (4) ◽  
pp. 663-667 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Fa-Chyi Lee ◽  
Deepti A. Singh ◽  
Daniel G. Haller ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Median Number ◽  
Phase Iii ◽  
Highly Active ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastric Cancer Patients

Purpose S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. Methods Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of ≥ 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. Results All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. Conclusion S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

Phase II Trial of 4′-Epi-Doxorubicin in Locally Advanced or Metastatic Gastric Cancer

1988 ◽  
Vol 74 (3) ◽  
pp. 313-315 ◽  
Author(s):  
Eduardo Cazap ◽  
Roberto Estevez ◽  
Mario Bruno ◽  
Daniel Levy ◽  
Carlos Algamiz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Future Studies ◽  
Phase Iii Trials

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4′-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

Imatinib 800 mg: Preliminary Results of a Phase II Trial of the GIMEMA CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1098-1098
Author(s):  
Gianantonio Rosti ◽  
Giovanni Martinelli ◽  
Fausto Castagnetti ◽  
Nicoletta Testoni ◽  
Giorgina Specchia ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Standard Dose ◽  
Phase Iii ◽  
High Dose ◽  
Molecular Response ◽  
Risk Patients

Abstract The conventional treatment of chronic myeloid leukemia (CML) in early chronic phase (ECP) is imatinib 400 mg daily. The estimated rates of major (MCgR) and complete cytogenetic response (CCgR) at 42 months are 91% and 84%, respectively (IRIS Trial - F Guilhot, ASH 2004), with a survival free from accelerated and blastic phase of 84%. The rates of CCgR are significantly different according to Sokal score, being 91%, 84% and 69% for low, intermediate and high risk categories. Phase I and II trials of imatinib have clearly shown a dose-response effect; more importantly, a single center phase II trial of imatinib 800 mg in ECP showed significantly better results vs standard dose, in terms of CCgR (90% vs 74%) and of complete molecular response (28% vs 7% at 18 months) [H. Kantarjian et al, Blood 103 (8), 2004]. The GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) CML WP is conducting a phase II trial of imatinib 800 mg in intermediate Sokal risk in ECP (trial CML/021). Overall, 89 pts (mean age 53 yrs) have been enrolled. Fourty-four patients completed 6 months of treatment: the complete hematological response rate is 100%; the MCgR and CCgR are 90% and 81%, respectively. The 6 months CCgR rate of this trial parallels the IRIS trial one in intermediate risk cases (84%), with a much shorter treatment period. The major molecular response rate at 6 months (RTQ-PCR as ratio BCR-ABL/ABL) is 56% (cut-off ≤ 0.12%) or 41% (cut-off ≤0.05%). The compliance to the treatment improved time by time, being 47% the patients receiving ≥ 80% of the scheduled dose between months 1–3 and 60% between months 4 - 6. A second project, exploring imatinib high dose, is reserved to high risk cases: a multinational working group, within the frame of Leukemianet CML WP, is conducting a phase III randomized trial (1:1) of imatinib 400 mg vs 800 mg in high Sokal risk in ECP. By July 31, 2005, 80 patients have been enrolled: GIMEMA CML WP (44 pts), Nordic Countries - Sweden, Denmark, Norway and Finland (25 pts), Turkey (10 pts) and Israel (1 pt).

NCRI CLL201 Trial: A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) with or without Rituximab in Previously Treated CLL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 752-752 ◽  
Author(s):  
Peter Hillmen ◽  
Christopher Pocock ◽  
Dena Cohen ◽  
Kim Cocks ◽  
Hazem A. Sayala ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Residual Disease ◽  
Early Death ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Color Flow ◽  
Randomized Phase Ii ◽  
Number Of Patients

Abstract Standard front-line therapy for chronic lymphocytic leukemia (CLL) is fludarabine plus cyclophosphamide. Adding mitoxantrone (FCM) or rituximab (FCR) appears to improve responses although no large randomized trials have been reported. We report a randomized Phase II trial of FCM and FCM-R in relapsed CLL. FCM was oral fludarabine (24mg/m2 for 5 days) and cyclophosphamide (150mg/m2 for 5 days) plus i.v. mitoxantrone (6mg/m2) on Day 1 of each cycle. FCM-R was identical with rituximab on Day 1 of each cycle (375mg/m2 cycle 1; 500mg/m2 cycles 2 to 6). Prophylaxis with aciclovir and co-trimoxazole was given. The primary end-point was response by NCI Criteria 2 months after therapy. Complete remission with incomplete marrow recovery (CR(i)) was defined according to the 2007 CLL Guidelines - clinical CR with a morphologically normal marrow but persistent cytopenias (i.e. platelets <100x109/l and/or neutrophils <1.5x109/l). In addition, minimal residual disease in the marrow was studied 2 months after therapy by four-color flow cytometry with MRD negativity defined as <0.01% CLL cells. 52 patients were entered into the trial with 26 in each arm. The median age was 65 (32–79) with 79% men. 42% had a β2m >4. The median number of prior therapies was 2 (1–6), 31 had prior fludarabine and 6 (12%) were refractory to or relapsed <6 months after fludarabine. 26/44 (59%) had unmutated VH genes (15/22 FCM-R; 11/22 FCM). 11 patients had deletion of 11q (FCM-R 5, FCM 6) and 1 patient had >20% 17p deleted cells (FCM-R). 36/52 (69%) received 4 or more cycles of therapy with no difference between FCM and FCM-R (18/26). Responses are shown in the Table. 35 SAE’s were reported in 23 patients. There was no difference in the number of patients with SAE’s between the arms (FCM 11, FCM-R 12). 6/7 patients (86%) who had 4 or more prior therapies reported an SAE, compared to 17/45 patients (38%) who had less than 4. 16 SAE’s were suspected to be related to FCM-R and 10 related to FCM. In summary, FCM-R is an effective therapy for relapsed CLL with over two-thirds of patients responding. The study design does not allow a statistical comparison between FCM and FCM-R but the results suggest that adding rituximab to FCM results in a higher complete response rate (CR + CR i = 43% for FCM-R and 13% for FCM) with more patients achieving MRD negativity (5 after FCM-R; 2 after FCM). The results of this randomised Phase II trial justify the study of FC with mitoxantrone and/or rituximab in larger randomized Phase III trials. Responses in 46 evaluable patients (remaining 6 not yet evaluable) All patients FCM FCM-R Number of patients 46 23 23 Overall response rate 29 (63%) 13 (57%) 16 (70%) CR 5 (11%) 1 (4%) 4 (17%) CR(i) 8 (17%) 2 (9%) 6 (26%) PR 16 (35%) 10 (43%) 6 (26%) SD/PD 12 (26%) 7 (30%) 5 (22%) Early Death (before assessment) 4 (9%) 2 (9%) 2 (9%) Withdrew consent (before assessment) 1 (2%) 1 (4%) 0 (0%) MRD negative 7 (15%) 2 (9%) 5 (22%)

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

A phase II trial of oral S-1 combined with gemcitabine in patients with unresectable biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15527-e15527 ◽  
Author(s):  
K. Nakamura ◽  
T. Yamaguchi ◽  
K. Sudo ◽  
T. Hara ◽  
T. Denda ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Bile Ducts ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Median Number ◽  
High Response Rate ◽  
Eligibility Criteria ◽  
Tract Cancer

e15527 Background: Optimal chemotherapy for unresectable biliary tract cancer is yet to be defined. We have conducted the phase II trial of Gemcitabine (GEM) with S-1, oral fluorouracil prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate to evaluate the activity and toxicity of such combination in patients with unresectable biliary tract cancer. Methods: Eligibility criteria were pathologically-proven biliary tract cancer, appropriate performance status 0 to 2, age 20 to 79 years, adequate hematological, renal and liver functions, no prior chemotherapy, and written informed consent. S-1 was given orally (30mg/m2) bid for 14 consecutive days and GEM (1000mg/m2) was given on day 8 and 15. Cycle was repeated every 21 days. Results: 30 patients with unresectable biliary tract cancer (Gall-bladder: intrahepatic bile ducts: extrahepatic bile ducts=7:16:7) were enrolled from March 2007 to December 2008. Patients characteristics were: median age; 67 (46–79), male/female; 20/10, PS 0/1/2; 16/13/1. Median number of cycles was 8 (range 1 to 14). Out of total 26 evaluable patients, objective responses were observed in 9 patients (30%); 16 patients achieved stable disease and 1 patients showed disease progression. Median survival was 390 days (95% c.i.: 290 - 490 days). The grade 3–4 toxicities observed were leucopenia (20%), neutropenia (40%), anemia (17%), thrombocytopenia (37%), anorexia (7%), fever (10%), rash (7%) and interstitial pneumonia (7%). Conclusions: The combination chemotherapy with GEM and S-1 was well tolerated and high response rate has been observed. This result is very promising but survival benefit against GEM monotherapy should be demonstrated in future phase 3 studies. No significant financial relationships to disclose.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8588-8588 ◽  
Author(s):  
David Samuel DiCapua Siegel ◽  
Paul Gerard Guy Richardson ◽  
Ravi Vij ◽  
Craig C. Hofmeister ◽  
Rachid C. Baz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Response Duration ◽  
Median Number ◽  
Open Label ◽  
Safety And Efficacy ◽  
Vein Thrombosis ◽  
Intent To Treat

8588 Background: MM-002 is a randomized, open-label, multicenter phase II trial evaluating the safety and efficacy of POM with or without LoDEX in advanced RRMM pts. Methods: Pts who had received ≥ 2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT), and were refractory to their last treatment were randomized to POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (according to EBMT criteria and investigator assessment), response duration, overall survival (OS), and safety. The efficacy outcomes are based on the intent-to-treat population (POM+LoDEX, n = 113; POM, n = 108). Results: The median number of prior therapies in each group was 5 (range 1–13). In the POM+LoDEX arm, 30 (27%) pts had high-risk cytogenetics, including del(17p13) and/or t(4p16/14q32). The overall response rate (≥ partial response) was 34% and 15% with POM+LoDEX and POM, respectively, with a median duration of 8.3 (95% CI: 5.8–10.1) and 8.8 (95% CI: 5.5–11.4) mos, respectively. At least minimal response was observed in 45% and 31% of pts, respectively. Median PFS was 4.6 (95% CI: 3.6–5.5) and 2.6 (95% CI: 1.9–2.8) mos with POM+LoDEX and POM, respectively, with a median follow-up of 16.0 and 12.2 mos. Median OS was 16.5 (95% CI: 12.4–18.5) and 13.6 (95% CI: 9.6–18.1) mos, respectively. The most common treatment emergent Gr 3/4 adverse events (AEs) reported in the safety population (n = 219) were neutropenia (44%), anemia (23%), thrombocytopenia (21%), and pneumonia (18%); there were no reports of Gr 3/4 peripheral neuropathy. The incidence of deep-vein thrombosis was low (2%). AEs were managed through dose reductions or interruptions, and supportive care with G-CSF (52%), RBC transfusions (47%), and platelet transfusions (17%). Discontinuations due to AEs were 10%. Conclusions: POM with or without LoDEX is clinically effective and generally well tolerated in RRMM pts who have received multiple prior treatments, including LEN and BORT. AEs were predictable and manageable. Updated data will be presented at the meeting. Clinical trial information: NCT00833833.

Docetaxel, Cisplatin, and Fluorouracil; Docetaxel and Cisplatin; and Epirubicin, Cisplatin, and Fluorouracil As Systemic Treatment for Advanced Gastric Carcinoma: A Randomized Phase II Trial of the Swiss Group for Clinical Cancer Research

2007 ◽  
Vol 25 (22) ◽  
pp. 3217-3223 ◽  
Author(s):  
Arnaud D. Roth ◽  
Nicola Fazio ◽  
Roger Stupp ◽  
Stephen Falk ◽  
Jürg Bernhard ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Infectious Complications ◽  
Phase Iii ◽  
Survival Times ◽  
Clinical Cancer Research ◽  
Advanced Gastric Carcinoma ◽  
Randomized Phase Ii

PurposeThis randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy.Patients and MethodsChemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status ≤ 1, and adequate hematologic, hepatic, and renal function randomly received ≤ eight 3-weekly cycles of ECF (epirubicin 50 mg/m2on day 1, cisplatin 60 mg/m2on day 1, and fluorouracil [FU] 200 mg/m2/d on days 1 to 21), TC (docetaxel initially 85 mg/m2on day 1 [later reduced to 75 mg/m2as a result of toxicity] and cisplatin 75 mg/m2on day 1), or TCF (TC plus FU 300 mg/m2/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL).ResultsORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens.ConclusionTime to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.

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